JP6639490B2 - Implantable devices - Google Patents

Description

  The present invention relates to an implant for position-selective capture of electrical signals of neurons propagating along at least one nerve fiber contained in a nerve fiber bundle and selective electrical stimulation of at least one nerve fiber Regarding possible devices. The implantable device includes an implantable electrode device that can be applied in a manchette fashion around a nerve fiber bundle to apply an electrical signal to selected nerve fibers within the nerve fiber bundle. Can be. Electrical stimulation is performed in animal or human patients, especially to have a targeted effect on blood pressure.

  Arterial hypertension is a typical lifestyle-related disease that has spread worldwide, threatening the lives of millions of patients and placing a heavy burden on health insurance systems. Therapeutic measures known hitherto are based on the administration of blood pressure lowering drugs, such as, for example, ACE inhibitors, beta blockers, etc. There are notable side effects such as slow heart rate, cardiac dysfunction, asthma attacks and the like. Furthermore, despite the development of new blood pressure lowering drugs, it has emerged that up to 30% of all patients with a corresponding medication cannot reach a reasonable target blood pressure. H. R. Contributed paper by HR Black et al., "Principal results of the controlled onset Verapamil invitation of cardiovascular end points (Conv., 208, J.T., 2A, 3A, 2A, 2A, 3A, 2A, 3A, 2A, 2A, 2A, 2A, 2A, 2A, 3A, 2A, 2A, 2A, 2A)

  Another treatment approach to address hypertension is Denistee. tea. Purafuta (Dennis T. T. Plachta), Oscar Kota (Oscar Cota), Thomas Gerhard Teak Ritz (Thomas Stieglitz), Mortimer Gières Tomyu Ren (Mortimer Gierthmuehlen) of paper "Selektive Ableitung und Stimulation fuer ein blutdrucksenkendes Implantat unter Verwendung von Vielkanal- Cuff-Electroden ", tm-Technisches Messen, 2013, Vol. 80 (5), published by the present applicant on pages 163-172. The findings obtained based on animal experiments conducted on rats were detected by using an electrode device implanted in a section of the nerve fiber bundle of the vagus nerve and by resolving the electrical signals of neurons from that section of the nerve fiber bundle. And the possibility of applying electrical signals to selected nerve fibers to technically stimulate blood pressure reduction. Thus, such vagal stimulation has the potential to be established as an alternative for treating essentially refractory blood pressure.

  The concept of selective vagus nerve stimulation relies on the experience of neuromodulation therapy for severe epilepsy, which has been applied and established for many years, and when epileptic seizures are beginning, The vagus nerve is electrically stimulated entirely using the implanted electrode device, at least to mitigate the intensity and duration. About this, F. F. Sidiqui, et al., "Cumulative effects of Vagus nervous stimulators on intractable seizures observed over 30 years old, three years, three years, three years, three years, and three years. See T. Stieglitz, "Neuroprothetik and Neuromodulation-Forschungsansaetze und klinischche Praxis bei thr zit zune zhe süh s s s s s g s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s s-s s s s s-either from the Governor's Office to the Governors.

  On the other hand, for chronic treatment of hypertension, it is important to first locate the blood pressure-related fibers by measuring techniques, and then selectively electrostimulate the fibers in a suitable manner. In order to minimize the burden on the vagus nerve by applying the electrode device by the implant and to excite the nerve sheath of the vagus nerve as little as possible, Dennis Tea. tea. A contribution by Dennis TT Plachta et al. Proposes the use of so-called cuff electrodes that can be attached to the vagus nerve outside the nerve. This has the advantage that the positioning of the cuff electrode along the vagus nerve is relatively easy, as well as that the surgery can be performed on the patient in a minimally invasive manner, ie without burden.

  Baroreflex is used for natural blood pressure regulation. Baroreflex is a self-regulating mechanism of homeostasis, and reflexly activates various effectors as blood pressure increases. In this case, in order to lower the blood pressure, the pulse rate is reduced, and the blood vessels of the artery are further expanded. In the case of hypotension, the baroreflex is suppressed, thereby increasing the pulse rate, narrowing the blood vessels and thus increasing the blood pressure again. The sensory input for the baroreflex is, inter alia, the so-called baroreceptors present on the wall of the aortic arch. From there, blood pressure information is monosynaptically delivered to the brainstem along nerve fibers related to blood pressure, referred to below as baroreceptive fibers. Above the threshold for blood pressure, the baroreflex triggers inhibition of sympathetic nerve fibers, which causes a direct drop in blood pressure. Shown in connection with FIGS. 2a and 2b, the English literature uses a manchette electrode, often referred to as a cuff electrode, to selectively detect pressure information sent to the brainstem and likewise selectively "overwrite" This baroreflex mechanism can be exploited by indicating to the brainstem a significantly elevated blood pressure situation, thereby causing a natural significant decrease in blood pressure.

  FIG. 2a shows a known manchette electrode E in a planar top view in a flattened state. FIG. 2b shows the manchette electrode E in the implanted state, in which the regions B1, B2 of the manchette electrode E are folded together for the purpose of space-saving form, as well as of the manchette electrode E. The support base region 1B provided with the first electrode device 2 holds one region of the nerve fiber bundle NFB in a manchette shape.

  The manchette electrode E consists of a flexible biocompatible support base 1, which in the realized embodiment is a polyimide film of about 11 μm thickness, of which, in the plane of FIG. In order to electrically stimulate individual nerve fibers NF running in the nerve fiber bundle NFB, a large number of individual electrodes are used to capture the electrical signals of the neurons on the upper surface of the supporting base. The configured first electrode device 2 is attached. As is evident in FIG. 2b, the support base 1 in the support base area 1B has been spontaneously oriented towards the nerve fiber bundle NFB by applying a mechanical film prestress accordingly. The individual electrodes of the first electrode device 2 come into direct surface contact with the nerve sheath EPI of the nerve fiber bundle NFB, as it wraps around forming the support base surface 1 ′, which is a straight cylindrical shape. Thus, the individual electrodes of the first electrode device 2 have a ring-shaped spatial shape that is curved in the circumferential direction U around the nerve fiber bundle NFB.

  For the position-selective acquisition of the electrical signals of the neurons and also for the selective electrical stimulation of the at least one nerve fiber NF, three axially spaced apart first and second axially identical ones are provided. One electrode structure 3 is used, the first electrode structure 3 comprising at least two first electrode surfaces 4 in the circumferential direction U, each in the illustrated exemplary embodiment according to FIGS. I have. The eight first electrode surfaces 4 belonging to the first electrode structure 3 are equally distributed in the circumferential direction U, that is, are arranged at an angular distance of 45 °. This allows a position selectivity divided into eight sections in the circumferential direction for position-selectively capturing the electrical signals of the neurons from the nerve fiber bundle NFB to be examined. The first electrode strips 5 which are arranged on both sides of the three first electrode structures 3 in the axial direction and completely embrace the nerve fiber bundle NFB in a ring shape are position-selective for electrical signals of neurons. The first electrode strip 5 serves as the anode or the opposite polarity, respectively, in the case of the electrical capture of the selectively selected nerve fibers NF in the nerve fiber bundle NFB. Work as

  A triple or triple of the first electrode structure 3, respectively, which is capable of capturing the electrical signal of the neuron monopolarly via the first electrode surface 4 or emitting the electrical signal for the purpose of site-selective stimulation, respectively. A tripolar device can identify impedance changes due to tissue growth at the metal electrode surface 4 and be removed by an evaluation technique, while on the other hand, the tripolar device along the axial direction of the corresponding nerve fiber NF Can be detected by appropriate tripolar amplification. In FIG. 2a, the above-mentioned first electrode structure which is mounted together on a support base surface 1 'facing the drawing plane and which is correspondingly terminated centrally via an electrical conductor L on a connection structure V 3 and a first electrode strip 5 each in the form of a ring, as well as a second electrode device in the form of a reference electrode 12 on the back side of the support base 1, the reference electrode 12 being on the one hand signal evaluation Used to capture the electrical background bulk signal or noise level in the body that underlies the ECG, on the other hand, opens up the possibility to capture the ECG signal using the Manchette electrode E. An electrode device which can be implanted as a manchette electrode E can be connected via an electrical connection structure V to a signal detection and generator 6 which is also formed as an implant and is hermetically encapsulated.

  Using a known implantable electrode device, what could be demonstrated within the framework of animal experiments in rats, a total of twenty-four, equally distributed around the nerve fiber bundle NFB and arranged in three poles The first electrode surface can capture the electrical time signal of the neuron, which is correlated with blood pressure, hereinafter referred to as the baroreceptive signal, but also the first electrode surface depends on its circumferential direction Is used to determine the location of baroreceptive nerve fibers. The stimulus applies to each of the triodes one or more electrode surfaces 4 of the first electrode structure 3 located in the middle of the triode device, which, upon detection, have respectively captured the maximum signal level of the baroreceptive signal. It was performed using. It has been demonstrated that selective stimulation of baroreceptive nerve fibers can clearly and reliably reduce blood pressure, in which case a very weak slow heart rate (60 minutes per minute). Less than one pulse) and almost insignificant slow breathing (less than twenty depressions per minute).

  In order to selectively electrically stimulate baroreceptive nerve fibers, an electrical stimulation signal based on a certain combination of fixedly set stimulation parameters is applied to each selected electrode surface 4 of a centrally located electrode structure. Applied to In this regard, the stimulation signal is applied to selected nerve fibers at freely selectable intervals in the form of electrical stimulation phenomena, e.g., every 20 seconds to generate electrical stimulation consisting of 100 single pulses. Was applied to the nerve fiber bundle via the respective selected electrode surface. Each single pulse has a stimulus pulse length of 0.6 ms and an anodic and cathodic stimulus amplitude of 0.8 mA each, which allows the electrodes to be polarized. The repetition rate of a single pulse, the so-called stimulation frequency, was 40 Hz, and the total length of a single electrical stimulation was 100 × 25 ms, or 2.5 seconds. In the rat stimulation experiments performed, various fixed stimulation parameters were used, i.e. 30-50 Hz stimulation frequency, 0.1 ms-0.5 ms stimulation pulse length, and 0.3 mA- A stimulation amplitude of 1.5 mA was used.

  The findings obtained in the context of previous animal studies suggest that electrical stimulation of baroreceptive nerve fibers can be highly promising to affect blood pressure, although it may be highly promising. The at least quantitative connection between the stimulus phenomena and the biological response in the form of blood pressure lowering that occurs based on organic regulatory mechanisms is still poorly understood. Especially in the case of animals larger than rats that have been used in animal experiments, or even more so in humans, the organically produced regulatory consequences are quantitatively determined, with more apparent in advance. It is important to provide a regulatory stimulus that is within the specified tolerance.

  The problem underlying the present invention is that the electrode device described above provides for the position-selective capture of electrical signals of neurons propagating along at least one nerve fiber contained in a nerve fiber bundle and at least one Implantable devices for selective electrical stimulation of nerve fibers can be used to significantly and more accurately influence certain areas of the autonomic nervous system, especially the vagus nerve, for the purpose of affecting blood pressure Is to develop it further. When appropriate regulatory measures are taken on organisms larger than rats, especially humans, the physiological and / or organic state of the targeted neurons is guaranteed to occur at least within predictable and quantifiable tolerances. Must have been. In addition, all measures necessary for this should not cause undesirable biological side effects. Basically, this device not only aims at affecting blood pressure, but instead or in combination with it, also optionally has other autonomous and sensorimotor state variables. Should be capable.

  A solution to the problem underlying the present invention is presented in claim 1. Features which advantageously further develop the solution idea are evident from the following description relating to the objects of the dependent claims and to the exemplary embodiments.

  Contrary to the procedure described above, the stimulation parameters, i.e. the stimulation pulse length, the stimulation amplitude, and the stimulation frequency, are each fixedly set and the at least one selected nerve fiber is electrically stimulated. The implantable device is applied to baroreceptive nerve fibers that are closely matched in shape, or time amplitude trajectory, to the pulse shape of the natural blood pressure signal, and overlap in time with the natural blood pressure signal. The natural blood pressure signal transmitted from the baroreceptors along the baroreceptive nerve fibers to the brainstem is overwritten according to the criteria. The stimulation according to the present solution is therefore not performed in a pulsating "on-off-on-off" manner as before, but rather a technical electrical stimulation signal applied along baroreceptive nerve fibers. Are transmitted to the brainstem at a stimulation frequency adapted to the natural signal rhythm, i.e., within a natural time window in which each brainstem expects a natural blood pressure signal.

  The natural shape of a pulse wave running through the baroreceptive field and within the aortic arch is that the pulse length is typically less than 1 second, as well as a strong, fast and non-linear rise of the pulse wave followed by a slow And is also characterized by a non-linear descent. This mechanical pulse wave is converted by the baroreceptors into the form of neuron electrical signals. The electrical signal of this neuron is transmitted to the brainstem via the vagus nerve and contains information on the strength and length of the mechanical pulse wave. The effect on the natural organic regulatory mechanism, technically caused by the use of implantable devices, is to adapt this natural neuron's electrical signal shape to at least one selected baroreceptive nerve fiber. This is done by temporally coherently overwriting the electrical time signal of the natural neuron with the applied technical electrical stimulation signal, and the amplitude level of this electrical stimulation signal depends on the desired therapeutic goal, It is higher or lower than the electrical time signal. In this way, there is no or significant excitement of the natural organic blood pressure regulation mechanisms, that is, the brainstem receiving the technically manipulated electrical stimulus signal will not be able to interact with the natural neuronal electrical time signal. I can't recognize the difference. This activates a natural, organic regulatory mechanism that produces a completely natural regulatory result featuring certain predictable forms of blood pressure regulation.

  In addition, the implantable device according to the present solution offers the possibility of monitoring blood pressure values to check independently, i.e. only when a significant deviation from the blood pressure reference value is confirmed, the natural organic Activate regulatory mechanisms. A further advantage is that the implantable device can be operated by means of a self-check, i.e. in the manner of a closed-loop function, in which the organic regulation results caused by the electrical stimulation are captured and evaluated, If necessary, readjust accordingly.

  For this purpose, the position-selective capture of the electrical signals of the neurons propagating along at least one nerve fiber, preferably a baroreceptive fiber contained in the nerve fiber bundle, and the selective capture of at least one nerve fiber The implantable device according to the present solution for efficient electrical stimulation features the following components:

  In the following, the device according to the solution will be described in connection with an example affecting blood pressure as a physiological parameter without limiting the comprehensive inventive idea. Of course, this implantable device may be used to affect other physiological parameters, such as respiratory rate, heart rate, body temperature, etc. In some cases, it can be used. The implantable device can be used on other peripheral nerves, or on nerves of the central or autonomic nervous system, to treat alternative bodily functions as well. As an example, the field of motor nerve replacement after central palsy when the spinal cord or brain is injured is mentioned. In these cases, pressure and posture receptors, for example sensory signals of the hand, can be selectively received by the implantable device and the grip force can be adjusted spontaneously according to the target value setting. In the field of neuromodulation, rehabilitation after stroke and hemiparesis using implantable devices is also promising. In this case, sensory signals can be amplified and coupled to improve the outcome of rehabilitation. Further conceivable are modulation of respiratory stimulators by implantable devices through the phrenic nerve at the diaphragm, modulation of the sympathetic nervous system at the sympathetic trunk, or efficient pain from highly selective peripheral nerve stimulation Treatment.

  A manchette around the nerve fiber bundle for position-selective capture of the electrical signals of the neurons along the selected nerve fiber within the nerve fiber bundle and also for selective electrical stimulation of at least one selected nerve fiber Provided is an implantable electrode device mounted on a biocompatible support platform, the support platform being oriented toward a nerve fiber bundle and being a straight cylindrical support when implanted. It has a base surface. In addition, a second electrode device for capturing an electrocardiogram signal representing the function of the heart is arranged on the biocompatible support base. The second electrode device does not necessarily have to be mounted on the same surface of the support base as the first electrode device described above.

  The implantable electrode device, in particular including at least the first and second electrode devices, is electrically connected to the evaluation / control unit or connectable to the evaluation / control unit. In the evaluation / control unit, the electrical signals of the position-selectively captured neurons and also the electrocardiogram signals can be evaluated in a time-resolved manner, whereby the neurons correlated with the blood pressure can be evaluated. Can be calculated. An evaluation / control unit formed as a digital signal processor or a microcontroller can process the signal data and generate control signals.

  A first comparison unit, which is connected to the evaluation / control unit, determines a characteristic and relative time lag between the electrocardiogram signal captured by the measurement technique and the neuron time signal correlated with blood pressure. Used to

  In this regard, the time interval between the R wave of the electrocardiogram time signal and the signal gradient point along the positively rising signal gradient of the time signal correlated with the blood pressure wave and captured by the measurement technique is defined as It is advantageous to determine. Depending on the configuration of the first electrode device, the time signal of the neuron, correlated with the pulse wave or blood pressure and captured by the measurement technique, often features a polyphase signal shape, which is characteristic of this signal shape. A signal slope point can be assigned, and this signal slope point is used to determine the time offset with respect to the electrocardiogram signal running immediately in time. The determined time lag between the electrocardiogram signal and the time signal correlated with the blood pressure or pulse wave or blood pressure wave and captured by the measurement technique then causes the generation of the technical stimulus signal to become baroreceptive. It is used to closely match in time the electrical signals of natural neurons that propagate along sexual nerve fibers.

  Furthermore, the evaluation / control unit determines a time window in which the time signal of the neuron correlated with the blood pressure is above a certain amplitude level, ie this time window corresponds to the pulse length of the blood pressure wave. The goal is to apply a technical electrical stimulation signal to at least one selected baroreceptive nerve fiber within this time window determined by the evaluation / control unit for the purpose of affecting blood pressure, This allows the brain to obtain an electrical stimulus signal of a signal length adapted to the length of the natural pulse wave at the time the brain expects a normal, ie natural, blood pressure signal.

  Furthermore, the evaluation / control unit is electrically connected to the first function generator, the first function generators each being determined by the evaluation / control unit and having a determined relative time offset with respect to the electrocardiogram signal. Within a time window, generate an electrical stimulation signal consisting of a number n of single pulses, the phase and temporal amplitude trajectory of which is calculated relative to a physiological parameter, preferably blood pressure The phase and amplitude trajectory of the time signal of the generated neuron is adapted. The electrical stimulation signal preferably differs only in the time-varying amplitude level, which in the case of hypertension treatment is greater than or greater than the amplitude level of the neuron's time signal which correlates with the natural blood pressure. Highly selected. The brain thus obtains information about the strongly elevated blood pressure, and a corresponding natural organic regulatory mechanism is activated for this strongly elevated blood pressure.

  A first function generator and a first electrode device of the implantable electrode device are also provided for converting and transferring the electrical stimulation signal in the form of a current signal composed of a number n of single pulses. Connected indirectly or directly via a signal-to-current converter, wherein the first signal-to-current converter outputs an electrical stimulation signal for selectively electrically stimulating at least one nerve fiber; Transmit to the first electrode device.

  Except for the implantable electrode device in which the first electrode device is in physical, ie electrical contact with the nerve sheath of the nerve fiber bundle, all the remaining components of the implantable device, ie the evaluation / control unit, the first The comparison unit, the first function generator and also the first signal-to-current converter are integrated in an implantable module, i.e. enclosed in a fluid-tight capsule by a biocompatible material. In this case, at least one electrical connection structure is provided for bringing the components assembled in the implantable module into electrical contact with the implantable electrode device.

  The selective electrical stimulation and the transmission of electrical signals of natural neurons along the selected baroreceptive nerve fibers are temporally coherently matched, and the signal length and shape of the stimulation signal are By adapting to the signals of the baroreceptive neurons, the difference is reflected only in that the time-varying amplitude levels are often higher, ie higher, than the natural baroreceptive signals. Of course, with the implantable device according to the present solution, it is also possible to apply a lower amplitude level to at least one selected nerve fiber. In order to quantitatively define the degree of technical raising or lowering of the amplitude level, the implantable device comprises at least one second comparison unit electrically connected to the evaluation / control unit, The second comparison unit compares at least one signal level assigned to the time signal of the neuron correlated with blood pressure with at least one reference signal, thereby generating a level difference value. An evaluation / control unit then defines at least a temporal amplitude trajectory of the stimulation signal, based at least on the determined level difference value, i.e., correlates with the blood pressure detected by the measurement technique using the implantable device. The time signal of a neuron significantly deviates from a predetermined reference signal, and thus the time-varying amplitude level of the electrical stimulus signal in response to adjustment requirements, the time signal of a neuron captured by a measurement technique and correlated with blood pressure. Higher or lower. In the case of hypertension treatment, it is usually important to have a significantly higher amplitude level that changes over time, so that information about the elevated blood pressure is sent to the brain, which is then raised Try to lower blood pressure levels within the framework of natural organic or biological regulatory mechanisms.

  The above-described electrical stimulation, performed using the Manchette electrode device illustrated in FIGS. 2a and 2b, sets isotropic signal direction coupling, ie, a defined signal propagation direction, along baroreceptive nerve fibers. Without this, the electrical stimulation signal can be propagated along afferent nerve fibers as well as along efferent nerve fibers. Signal propagation of electrical stimulation signals along efferent nerve fibers, i.e., to the heart, without significant lasting effects on non-baroreceptive afferent and efferent nerve fibers within the nerve fiber bundle. For blocking, a manchette electrode device which is a modification of the electrode device described in FIG. 2 is suitable, which includes a unidirectional electrical connection along at least one selected nerve fiber in the nerve fiber bundle. At least one third electrode device configured to inhibit signal transmission has been added.

  A third electrode device, also mounted on the same support platform surface of the same integrally connected support platform as the first electrode device, selectively positions baroreceptive nerve fibers within the nerve fiber bundle. Present in a spatially fixed assignment with respect to the first electrode device capable of capturing and also selectively electrostimulating, in particular the first electrode surface of the at least three first electrode structures. I have. The third electrode device grasps the located baroreceptive nerve fibers and, in order to suppress the transfer of electrical stimulation signals along the efferent, ie, nerve fibers to the heart, the baroreceptive nerve fibers Can be used for the purpose of inhibiting selectively. For this, at least two, preferably four or more, second electrode surfaces of at least one third electrode structure are used, the second electrode surface being one of the at least three first electrode structures. Like the first electrode surface, it is similarly distributed in the circumferential direction of the surface of the support base, which is oriented toward the nerve fiber bundle and is formed in a straight cylindrical shape. In order to inhibit the localized efferent baroreceptive nerve fibers, at least one of the third electrode surfaces of the third electrode structure is electrically activated, whereby the efferent nerve fibers are targeted. Time-limited and selectively inhibited. In this case, from at least one activated third electrode surface, an electric polarization field enters the nerve fiber bundle and interacts mainly with the nerve fiber to be inhibited. In order to axially limit the electric polarization field propagating in the nerve fiber bundle during inhibition, a second electrode strip is used, which is mounted on each of the axially opposite sides of the third electrode structure, The electrode strip is a ring electrode completely surrounding the nerve fiber bundle in the implanted manchette electrode.

  This modified implantable electrode device is provided with an additional third electrode device for inhibiting selected efferent nerve fibers, along the nerve fiber bundle and toward the heart or baroreceptor. That is, the first electrode device, which is directed caudally, and selectively captures the electrical signals of the neurons and also electrically stimulates the localized nerve fibers, is directed toward the brain, or rostrally. Can be applied to nerve fiber bundles.

  With a third electrode device, inhibition can be achieved either by means of a so-called anode block or by applying a sinusoidal signal whose frequency is in the kilohertz range. In the case of an anode block, at least one of the second electrode surfaces is polarized to the anode, thereby generating a dominant potential at the location of the efferent nerve fiber, which activates the corresponding nerve fiber. Stimulation is suppressed. Inhibition can also be achieved by applying a high-frequency signal, in which case a high-frequency electrical inhibition signal is applied to at least one selected third electrode surface, thereby providing efferent nerve fibers. The electrical signaling mechanism along is temporarily stopped.

  In both cases, the third electrode device provided by the solution acts spatially axially restricted, this restriction being given by the axial distance of both third electrode strips. And the third electrode strip is spatially close to the first electrode structure, but anyway, the implantable electrode device does not exceed the axial length of 4 cm and the centrifugal It is desirable to be spatially constrained in the axial direction along the nervous nerve fibers, so that the first electrode device placed on the brain side along the nerve fiber bundle, without being affected by the inhibition mechanism, Electrical stimulation signals to the brain can be coupled to the localized afferent nerve fibers. In this way, any side effects due to the possibility of direct stimulation down to the heart, ie in the direction of efferent nerve fibers, can be eliminated.

  Advantageously, the third electrode surface of the third electrode structure is equally distributed along the imaginary loop line in the implanted manchette electrode, so that the periphery of the nerve fiber bundle Efferent nerve fibers localized against are selectively and effectively inhibited.

  However, in an advantageous manner, the shapes and the sizes of the third electrode surfaces are not necessarily identical to one another, in that the axial extent of the third electrode surfaces is each equal to the first three electrode structures. Is selected to be the same as that of the first electrode surface in the axial direction. The circumferential extent of each of the third electrode surfaces is selected to be greater than the circumferential extent of the first electrode surfaces. Therefore, the third electrode surface preferably has a larger area than the first electrode surface, so that the position selectivity by which the third electrode surface can electrically polarize a particular efferent nerve fiber is reduced by the first electrode surface. The plane is smaller than the position selectivity that can electrically stimulate the localized nerve fibers. As an alternative, the third electrode surface may be formed as a circular surface instead of a rectangle. This has the advantage that potential field tips due to local, edges or corners are not formed.

  The third electrode device is preferably formed in the form of a three-electrode device, ie the third electrode structure has a third electrode strip formed on each side in the axial direction, each in the form of a ring. In this connection, the axial distance along the support base between both third electrode strips is preferably between 0.5 cm and 3 cm, especially between 0.75 cm and 1.25 cm Has been selected. The axial extension of the ring-shaped third electrode band is preferably between 1 μm and 5 mm, and more preferably between 100 μm and 4000 μm.

  The third electrode surface of the third electrode structure is arranged axially in the middle between both third electrode strips, and the axial distance to the second electrode strip is respectively the third electrode strip. It has an axial extent that is greater than the axial extent of the surface itself.

  Especially with regard to the possibility of carrying out the depolarization measures, instead of one third electrode structure, the axial direction between the third electrode strips, like the formation of the respective first electrode structure in the first electrode device. It is conceivable to arrange three third electrode structures spaced apart from each other. It should be noted that for completeness only, more than three first and third electrode structures may likewise be arranged between the respective first and third electrode strips. . That is, three, five, seven or more odd first and / or third electrode structures could be provided.

  In one preferred exemplary embodiment, one third electrode structure includes four third electrode surfaces, each of which has an electrode area of one third electrode band. It is selected to be less than one quarter of the area. The first or third electrode strip provided on the first and third electrode devices is used as a ground pole or an opposite pole, respectively, for polarization of the first or third electrode structure. For reasons of relationship, the areas of the first and third electrode strips are each selected identically. However, in the formation of the first and third electrode strips, individually and independently selected areas can be assumed.

  Further, all the electrodes of the third electrode device, ie, the third electrode surface and the third electrode band, have an electric conduction capacity having a smaller charge transfer capacity than the electrode material forming the first electrode surface of the first electrode device. It has proven to be advantageous to make them from conductive materials. Iridium oxide is used as a particularly suitable material with a particularly high charge transfer capacity for forming the first electrode surfaces of the first electrode device, respectively, whereas the third electrode surface and the third electrode band The material is made of platinum or an electrically conductive polymer.

  All the electrode surfaces of the first and third electrode devices are preferably formed flush with the support base surface of the support base, or are arranged so as to sink below the support base surface, so that the electrode surface is It does not protrude from the surface of the support base and makes surface contact with the nerve sheath of the nerve fiber bundle as little as possible. Due to the non-invasive surface contact, the implantable electrode device can be easily applied and positioned along the nerve fiber bundle in surgery, with little or no excitement of the nerve sheath.

  In addition, to address the tissue excitability and inflammatory response resulting from implanting, a biocompatible polymer support base may provide an agent that inhibits the inflammatory response, at least in the area of direct surface contact with nerve fiber bundles. It is proposed to have A further measure to reduce the mechanical excitement of nerve fiber bundles that can be caused by surface contact with the manchette-like manchette electrode involves rounding the axial boundary edges of the support base surrounding the nerve fiber bundle. In particular, in the region of the support base surface, in which the biocompatible support base is oriented towards the nerve fiber bundle and is a straight cylinder, the base thickness of the support base is larger than the other support base areas, respectively. It has edge regions facing each other in direction, which edge regions have rounded edge edges.

  A further preferred embodiment comprises at least one, preferably a plurality of light guide openings or apertures in the region of the third electrode device used for the electrical inhibition of the localized nerve fibers, Light can be applied or coupled through the mouth or aperture through the nerve sheath of the nerve fiber bundle. The optical waveguide is disposed axially adjacent to both second electrode strips, and the shape, size and dispersion mimic the third electrode surface of the third electrode structure. Is preferred. By providing a plurality of spatially separated optical waveguides on the surface of the support base so as to lead to the nerve fiber bundle, the nerve fiber bundle is activated in order to photoactivate the optogenetic response of neurons within the nerve fiber bundle. Within, uniform or different optical signals can be applied at different wavelengths. In this way, a large number of appropriately arranged light outlets or apertures can cause the activation or inhibition of neurons within the nerve fiber bundle to be activated in a position-selective manner, these reactions being carried out via the electrode surface. This can be done instead of or in addition to the neuronal process that is triggered.

  As already mentioned, the implantable electrode device formed according to the present solution is applied along the nerve fiber bundle such that the third electrode device is in the direction of the heart along the nerve fiber bundle. It is important to. In this way, efferent nerve fibers can be inhibited, whereas the first electrode device, which is directed along the nerve fiber bundle towards the brain, has a localized afferent, It is guaranteed that it can be used for the purpose of selectively stimulating nerve fibers leading to it. If there is a need to selectively inhibit afferent nerve fibers, a modified implantable electrode device can be implanted that is oriented backwards along the nerve fiber bundle. A further possible embodiment comprises a second inhibitory third electrode device, wherein the second third electrode device is in the third axial direction of the first electrode device. It is mounted next to and opposite to the electrode device.

  Furthermore, implanting an electrode device in a body surrounding a nerve fiber bundle in a manchette shape faces the fundamental problem that the electrode strip and the electrode surface mounted on the polyimide support base are constantly exposed to a moist environment. This can result in degradation phenomena, especially at the planar joints between the electrode surfaces and the polyimide support base, which cause local delamination and consequently at least contact degradation, thereby resulting in a final Specifically, the electrical efficiency of the electrode device decreases. To address this delamination phenomenon between the metal electrode surface and the polyimide support base due to the environment, in a preferred embodiment, at least the first and third electrode strips each have at least one local opening. The first and third electrode strips are planarly coupled to the support base or the support base surface such that the polymer or polyimide forming the support base at least partially penetrates the at least one opening. I have. This improves the mechanical locking between the respective electrode strips and the support base.

  A further possibility for a long-term stable connection between the electrode surface or electrode band and the biocompatible polyimide or polymer material of the support base is a special form of electrode surface or electrode band and thereby possible This is reflected in the special incorporation of the special electrode into the support base. To this end, inter alia, the first and third electrode strips each have a metal substrate, which has flat upper and lower surfaces and at least projects locally perpendicularly to the upper surface of the substrate. It comprises one, preferably a number of structural elements, which are preferably formed in the form of columns, ribs, sleeves or girders. The metal substrate is completely covered by the biocompatible polymer of the support base except for a first surface area of the at least one structural element that is oriented toward the support base surface and does not protrude from the support base surface. Besieged. This reduces the freely accessible electrode contact surfaces on the support base surface, but except for the surface area oriented towards the support base surface, based on the hermetically enclosed enclosure of the substrate and the structural elements integrally connected to the substrate. , Completely surrounded by the biocompatible polymer of the support base. The penetration of liquids or moisture due to the environment between the electrode strip and the biocompatible polymer of the support base becomes considerably more difficult, whereby the degradation phenomena can be largely eliminated. In a further preferred embodiment, preferably between the lower surface of the metal substrate and the biocompatible polymer of the support base is attached an adhesion-mediating layer or an adhesion-mediating layer configuration that counteracts the possibility of moisture-induced delamination phenomena. I have.

  The implantable device according to the present solution comprises a position-selective capture of at least one electrical signal of a neuron propagating along at least one nerve fiber encapsulated in a nerve fiber bundle of the human or animal body and at least one It would be advantageous to be able to implement a method for selective electrical stimulation of nerve fibers. In particular, in the case of electrical stimulation of afferent nerve fibers, that is, nerve fibers that transmit the electrical signals of neurons to the brain, this solution can not distinguish between electrical signals of natural neurons and electrical stimulation signals, especially in the brain. Do not cause any or significant excitation of brain function. The method according to the solution features the following process steps.

  First, it is important to selectively capture the electrical signals of neurons that propagate along the nerve fibers to be affected. This step can be performed by an electrode device known per se. Based on the captured natural neuron electrical signal, an "artificial" electrical signal is generated whose signal length and temporal amplitude trajectory correspond to the captured natural neuron electrical signal. Modification of the "artificially" generated electrical signal by increasing or decreasing its amplitude within at least a temporal portion of the signal length of the electrical signal in response to a therapeutic goal setting, e.g., a decrease or increase in blood pressure. I do. Preferably, the temporal amplitude trajectory of the electrical signal is raised or lowered uniformly over the entire length of the electrical signal, ie over the entire signal length. This measure results in an electrical stimulation signal that is applied to nerve fibers in temporal phase with the electrical signal of the neuron. This means that the electrical signals of the natural neurons are temporally coherent by one electrical stimulation signal, that is, correspond to the temporal signal length of the electrical signals of the natural neurons and the temporal order along the nerve fibers. Means that it will be overwritten. This temporally coherent overwriting process replaces the information inherent in the natural neuron electrical signal with the information imprinted on the artificially generated electrical stimulation signal.

  The electrical stimulation signal propagates along the afferent nerve fibers in the same temporal order and the same temporal signal length as the signal of the original neuron. Can not.

  In order to avoid that the electrical stimulation signal applied to each nerve fiber propagates in both directions along the nerve fiber, the electrical stimulation signal is applied before and / or during the time when each electrical stimulation signal is applied to the nerve fiber. Preferably, an electrical inhibition signal is applied to the nerve fiber so that the electrical stimulation signal can only propagate in one direction along the nerve fiber. The suppression of signal propagation in the direction of the undesired nerve fibers is preferably effected by an additional electrode device separate from the electrode device used to electrically apply the electrical stimulation signal, wherein the additional electrode device is , Attached along the nerve fiber to the location where the electrical stimulation signal is to be applied, on the opposite side of the direction of propagation of the electrical stimulation signal.

  In the following, all further features which advantageously form the implantable device will be described with reference to the figures.

  Hereinafter, the present invention will be described by way of specific examples with reference to the drawings based on exemplary embodiments without limiting the comprehensive inventive idea.

FIG. 2 is a block diagram for illustrating all components of an implantable device according to the present solution. 1 shows an implantable electrode device according to the state of the art. 1 shows an implantable electrode device according to the state of the art. FIG. 4 is a timing diagram for illustrating a neuron time signal that is correlated with an electrocardiogram signal and blood pressure. It is a figure for explanation of a stimulus signal composed of n single pulses, and explanation of one single pulse. FIG. 7 illustrates two alternative modes of operation of an implantable device for blood pressure regulation. FIG. 4 is a schematic plan view of an implantable electrode device with a third electrode device for inhibiting selective nerve fibers. 7a shows an electrode strip with an opening, 7b is a detailed view of an electrode strip incorporated in a support base, and 7c shows an alternative formation of a structural element. FIG. 4 illustrates a manchette that additionally enhances an implantable electrode device. FIG. 4 illustrates a manchette that additionally enhances an implantable electrode device. FIG. 4 illustrates a manchette that additionally enhances an implantable electrode device. FIG. 4 illustrates a manchette that additionally enhances an implantable electrode device. FIG. 4 illustrates a manchette that additionally enhances an implantable electrode device. FIG. 4 illustrates a manchette that additionally enhances an implantable electrode device. FIG. 2 shows a hydraulic application structure of an implantable electrode device. FIG. 4 is a flowchart for performing electrical stimulation of nerve fibers.

  FIG. 1 is a block diagram showing the individual components of an implantable device, each of which is interconnected via a mostly bi-directional electrical communication path (see indication of connection arrows). I have. The individual communication paths can be implemented in the form of wired or wireless connection paths, via which electric signals can be transmitted in both directions for informal data transmission and also for electric energy transmission. is there.

  The main components of the implantable device correspond to the implantable electrode device E, the evaluation / control unit A / S, the first comparison unit K1 electrically connected to the evaluation / control unit A / S, and so on. A first function generator F1 connected to the evaluation / control unit A / S and a first function generator indirectly or directly also connected to the first function generator F1 and electrically connected to the implantable electrode device E Is a signal-current converter SSW1.

  In a first embodiment, the implantable electrode device E corresponds to an electrode device known per se applicable as a manchette around a nerve fiber bundle and illustrated in FIGS. 2a, 2b. For this purpose, a first electrode structure 3, preferably formed as a triode device, is provided for the purpose of selectively detecting the time signal of an electrical neuron, wherein the first electrode structure 3 is provided. Are respectively limited on both axial sides by an annular first electrode strip 5 in the implanted state (see FIGS. 2a and 2b).

  The implantable electrode device E additionally comprises at least one electrode for capturing an electrocardiographic signal, such an electrocardiographic signal pickup comprising, for example, a reference electrode 12 based on the implantable electrode device illustrated in FIG. 2a. Is possible.

  The electrical information detected by the electrode device E, which is related to both the electrocardiogram signal and the electrical time signal of the neuron correlated with the blood pressure, is time-resolved and evaluated / control unit A / S for further evaluation. Sent to A timer unit T is preferably used for time-resolved capture of the electrical signal and transmission to the evaluation / control unit A / S. To better understand the mode of operation of the implantable device, with reference to FIG. 3, an electrocardiogram signal (see A) captured by a second electrode device applied around the vagus nerve in the area of the carotid artery; For example, a natural pulse wave or blood pressure wave PW (see B) by the aorta, which can be captured by a dedicated blood pressure sensor in the aorta near the heart, and a neuron time signal calculated from the neuron electrical signal and correlated with the blood pressure. The time relationship with ZS (see C) is shown.

  The mechanical pulse wave PW excites the baroreceptors in the aortic wall, which in turn emit frequency-encoded electrical signals of neurons according to the strength of the pulse wave PW. All of this synchronized excitation of hundreds of baroreceptors combine to generate a neuronal electrical signal that can be picked up via a Manchette electrode applied around the vagus nerve.

  However, technical stimulation of the vagus nerve for the purpose of therapeutically overwriting the electrical signals of natural neurons directed along the vagus nerve to the brain takes into account at least two temporal delay effects. This time delay effect should be taken into account during technical stimulation, especially since the stimulation should be as natural as possible to avoid the brain being continuously excited by this technical signal intervention. Or it is important to compensate.

  This, on the one hand, relates to the time lag ZV between the beginning of the electrocardiogram signal or the R-wave of the electrocardiogram signal (see FIG. 3A) and the rise of the blood pressure wave PW in the aorta (see point P1 in FIG. 3B). On the other hand, it relates to the time lag ZV * between the baroreceptor excitation and transduction and the neuronal electrical time signal ZS until the Manchette electrode E reaches the area where the natural blood pressure signal should be overwritten. This time shift ZV * typically selects between point P1 and the first maximum M of the neuron's electrical time signal ZS.

  The electrical time signal ZS of a neuron can appear in various ways, and is generally in the form of a so-called "Mexican hat", and thus consists of a plurality of "swings". This seems strange at first, especially since the pulse wave signal PW is not coded into a "waveform" by the baroreceptors. The reason for this lies in the triode configuration of the first electrode device. In other words, the electric pulse wave signal of the “unimodal” natural neuron passes through the three electrode structures of the first electrode device in the longitudinal direction along the vagus nerve, and sequentially passes through the three electrode structures. Can be polarized. Thus, the electrical signal of the single-phase neuron is converted into the electrical time signal ZS of the multi-phase neuron.

  In addition, the calculated electrical time signal ZS of the multiphase neuron is temporally between the characteristic gradient rising point P1 and the gradient falling point P2 of the pulse wave PW, that is, the duration of the pulse wave PW. Is always within a time window T1 corresponding to

  In view of the temporal lags ZV and ZV * described above, an electrical stimulation signal is generated within the time window ZF (see FIG. 3D) to selectively stimulate at least one baroreceptive nerve fiber. It is important to apply to the vagus nerve via the first electrode device for the purpose.

  The determination of the electrical time signal ZS of the neuron correlated with blood pressure (see FIG. 3C) differs from the capture and measurement technical use of the electrocardiogram signal, in that the time signal correlated with the blood pressure measured with the measurement technology Since the signal level of ZS cannot be distinguished from the surrounding electric noise level, special signal processing or signal processing is required. In this regard, it is preferred that the electrical signal of the neuron obtained by the implantable electrode device be coherently averaged, preferably with the electrocardiogram signal as a trigger, wherein all signal components that follow blood pressure reproducibly are Is additionally amplified. For further details on this, see Dennis Tea, cited at the outset. tea. Purafuta (Dennis T. T. Plachta), Oscar Kota (Oscar Cota), Thomas Gerhard Teak Ritz (Thomas Stieglitz), Mortimer Gières Tomyu Ren (Mortimer Gierthmuehlen) of theses "Selektive Ableitung und Stimulation fuer ein blutdrucksenkendes Implantat unter Verwendung von Vielkanal -Cuff-Electroden ", tm-Technisches Messen, 2013, Vol. 80 (5), pp. 163-172.

  In FIG. 3C, the time lag ZV with respect to the electrocardiogram signal (see FIG. 3A) is determined by using the electrical time signal ZS of the neuron, which is indicated by the time-varying amplitude trajectory and is correlated with the blood pressure. can do. Here, the electrical time signal ZS of the neuron correlated with blood pressure, which can be determined by the implantable device, only corresponds to the relative blood pressure value, ie, since the potential rises and falls with blood pressure. Note, on the other hand, that the time signal maxima are not absolute blood pressure in units of mmHg. Therefore, determining the absolute blood pressure value requires the provision of an additional external or internal reference sensor capable of capturing the absolute blood pressure. For the purpose of calibrating the time signal ZS obtained by the implantable electrode device, technical implantable blood pressure sensors, which are also implantable, such as tip catheters known per se, or extracorporeal blood pressure manches, are suitable. Is preferred. FIG. 1 shows the reference blood pressure sensor SB for this purpose as a further component, which need not necessarily be formed as an implantable unit. The absolute blood pressure value determined by the reference blood pressure sensor SB is also preferably time-resolved and transmitted to the evaluation / control unit A / S. A clock UH that exchanges data with the reference blood pressure sensor SB is used for the corresponding time capture.

  The electrical stimulation of baroreceptive nerve fibers in the nerve bundle held in a manchette manner by the implantable electrode device E as required for efficient blood pressure treatment is correlated with the electrocardiogram signal and blood pressure. It is necessary to analyze the electrical time signal of the neuron. The evaluation in this regard is made in the evaluation / control unit A / S with the aim of precisely determining when the brain expects baroreceptive signals transmitted via baroreceptive nerve fibers. In addition, the technical electrical stimulation of the nerve fibers transmitting the blood pressure signal should match the natural blood pressure signal sent, in terms of time, duration, and also qualitatively time-varying signals. As a timer signal or a trigger signal, for example, the electrocardiogram signal is captured as a monopolar artifact via the reference electrode 12 (see FIG. 2a) and transmitted as a time signal to the evaluation / control unit A / S. Thereafter, the evaluation / control unit A / S determines a time lag ZV between the electrocardiogram signal and the natural pulse wave PW. For this purpose, in particular, the time difference between the R-wave of the electrocardiogram signal and the characteristic signal gradient point P1 along the rising initial gradient of the blood pressure wave PW is used. The time lag ZV is <200 ms for a human at a normal pulse (65 BPM) (see FIG. 3A, time axis in seconds). Furthermore, within the framework of the evaluation / control unit A / S, the characteristic pulse length T1 of the pulse wave PW is measured, the pulse length T1 being along the first signal gradient point P1 and the descending signal gradient. It is given by the time interval with the second signal gradient point P2.

  Furthermore, in the evaluation / control unit A / S, biologically conditioned delays, for example the conversion of mechanical events (pulse waves) into bioelectric signals and / or the conversion of technical current signals into bioelectric signals The corrected time lag ZV * is determined taking into account the conversion of the potential neurons to potential and / or the time lag caused by the characteristic transmission speed along the neuron fibers, and this time lag is determined. ZV * is taken into account when generating the stimulus signal.

Thus, it is important to electrically stimulate at least one baroreceptive nerve fiber within a specific time window ZF with a defined time lag ZV + ZV * relative to the captured electrocardiogram signal. This is carried out by a function generator F1, which consists of a number n of single pulses, whose phase and temporal amplitude trajectories are correlated with the natural blood pressure and the electrical signal SN of the neuron (FIG. 4A) is generated. In this connection, the duration T _SN and the amplitude shape of the electrical signal Sn of the natural neuron propagating along the baroreceptive nerve fiber are similar to the shape and pulse length of the blood pressure or pulse wave PW. Please note.

This function generator F1 is composed of n single pulses EP (in FIG. 4A, the stimulus signal SSI is composed of 13 single pulses EP, and in fact, one hundred to two hundred single pulses Modulate the amplitude of the stimulus signal, thereby approximately forming the biological pressure trajectory captured by the implantable electrode device E as a wrapper function in the stimulus signal SSI. In order to define the time-varying amplitude trajectory of the stimulus signal SSI, ie the mutually synchronized amplitude of the single pulse EP in one stimulus signal, the pulse length T1 and the time signal ZS of the time signal ZS correlated with the blood pressure. _Is used. The pulse length T1 and the maximum amplitude _Amax are advantageously determined in the first comparison unit K1.

  Each single pulse EP has a characteristic eigenvalue that is evident from FIG. 4B. That is, each single impulse EP has a signal portion KT on the cathode side and a signal portion AT on the anode side. The anode-side signal portion AT of each single impulse EP has an anode-side amplitude E1 of ampere and an anode-side pulse width E4. The cathode-side signal portion KT also has a cathode-side amplitude E2 and a cathode-side pulse width E3 of ampere. The repetition rate E5 is measured in Hz. The repetition rate E5 does not necessarily correspond to a fixed frequency, but rather if the external electrical activation follows or corresponds to the natural typical pattern of activity by neurons, ie It has been found that the neuron system, ie the neuronal nerve fibers, can be best stimulated when subject to a distribution function, preferably a Poisson distribution. The generation of the stimulus signal SSI composed of a number n of single pulses EP is achieved by means of a first function generator F1 in which both phases of each single pulse EP, namely the signal part AT on the anode side and the cathode side Is preferably performed so that the area of the signal portion KT is the same. Otherwise, at least the electrode contacts, ie at least the electrode surfaces 4 (see FIG. 2) of the tripolar electrode structure 3, are polarized, so that subsequent electrical stimulation is significantly less effective in the nerve fiber bundle. Because it could be applied to at least one selected nerve fiber. In addition, polarization produces a DC potential that, when this DC potential crosses the window of water, can cause charge imbalance to cause corrosion by redox reactions. The individual anode-side and cathode-side signal portions AT, KT of each single pulse EP are generated in the form of rectangular partial signals by a first function generator F1.

  In addition, the degree of "roundness" in the signal gradient of each single impulse EP has an advantageous effect on the reduction of the corrosion effects occurring at the metal contacts of the individual electrodes of the implantable electrode device, Has the advantage that the lifetime of the implantable electrode device can be improved. Such a technical signal gradient rounding of the repolarization gradient E6, illustrated in particular in the schematic diagram of FIG. 4B at the lower left, not only improves the electrochemical properties described above, but also at least one selected It also has a positive effect on the biological effectiveness of electrically stimulating nerve fibers. For this purpose, a first modulator M1 is connected immediately after the first function generator F1 (see FIG. 1). The modulator M1 can, inter alia, make the rectangular repolarizable signal part AT longer or smoother in time with respect to the polarizable signal part KT, both signal parts AT, KT having complete electrode surfaces. The signal is uniform so that it can be repolarized, ie, the signal strength is the same. As an alternative or in combination with the above measures for rounding at least the repolarizable signal part AT, a further advantageous effect of the first modulator M1 on each individual single pulse EP generated by the first function generator F1 is provided. The effect is to decouple temporally the signal part KT on the cathode side and the signal part AT on the anode side by a temporal interruption E7 (see FIG. 4, lower right display). This avoids extremely long signal gradients between the cathodic and anodic signal portions KT, AT, thereby eliminating unwanted neurostimulatory artifacts. Of course, in addition to this, the time length of the interruption E7 can be modulated.

  All of the single pulse features E1 to E7 described above and apparent from FIG. 4 can be individually tuned and adjusted with each other by the first modulator M1.

  The implantable device should apply the electrical stimulation signal SSI to at least one baroreceptive nerve fiber at any time and at any strength and length, depending on individual regulatory requirements, for the purpose of leveling blood pressure Can be determined voluntarily. For this purpose, the implantable device according to FIG. 1 is provided with at least one second comparison device K2 which is electrically connected to the evaluation / control unit A / S. A second comparison device K2, which can be formed structurally together with the first comparison unit K1, determines at least one characteristic signal level of the neuron time signal ZS that is correlated with the blood pressure by an evaluation / control unit A / S and a comparison signal which is preferably stored in a lock-up table LT connected to the comparison unit K2, and generates a characteristic level difference, on the basis of which level evaluation / control unit A / S defines at least a temporal amplitude trajectory of the stimulus signal SSI, that is, a time-varying amplitude level. Finally, it is advantageous, at least on the basis of this generated level difference value, to be able to variably tune all the stimulation parameters E1 to E7 with respect to each other, and thus to apply at least one baroreceptive nerve fiber. All single pulse shapes can be individually selected to construct the stimulus signal SSI to be performed.

  Of course, it is advantageous that not only the reference signal stored in the lock-up table LT, but also additional information characterizing the physiological condition of each patient can be stored for the purpose of electrically stimulating at least one baroreceptive fiber. Yes, for example, information that characterizes the patient's exercise status, level difference values, captured absolute blood pressure, and the like.

  The implantable device is therefore provided in one advantageous embodiment with an acceleration sensor BS, which is preferably incorporated in an implantable module, in which the evaluation / The control unit A / S, the first and second comparison units K1, K2, the first function generator F1, and the first signal-to-current converter SSW1 are combined. The acceleration sensor BS is electrically connected to the evaluation / control unit A / S, so that the generated acceleration information can be transmitted to the evaluation / control unit A / S for further evaluation. An acceleration sensor mounted outside the patient's body may be used and the acceleration information of the acceleration sensor can be sent to the evaluation / control unit A / S wirelessly, for example by inductive data coupling. Thus, at least one preferably tri-axial acceleration or motion sensor BS can capture the physical activity of the respective patient, thereby taking into account the increase in blood pressure due to the motion, The resulting increase in blood pressure is recognized from the side of the implantable device itself and does not lead to a corresponding hypotensive stimulation of at least one baroreceptive nerve fiber.

  It is advantageous to be able to form and mount a triaxial acceleration or motion sensor outside the body, as well as to be provided with further external units, for example an energy source ES, a memory module SM, and a signal and energy supply unit SES. is there. The transmission of all electrical signals and also the transmission of electrical energy uses signal and energy transmission techniques based on wireless guidance.

  All information transmitted to the evaluation / control unit A / S, that is, the time signal ZS of neurons, inter alia captured and correlated with blood pressure, and also all externally transmitted information, are stored in the lock-up table LT. And the corresponding adjustment mechanism underlying the implantable device can always retrieve updated information. In this way, for example, a time signal ZS of neurons picked up by the electrode device E and correlated with blood pressure, which merely represents a relative blood pressure signal, can be captured by the latest or absolute blood pressure measurement system SB inside or outside the body. Can be calibrated by the target blood pressure value. Furthermore, the implantable device formed according to the present solution can at least capture the organic feedback of the stimulation performed using the electrode device E and thus achieve a so-called “closed-loop regulation function”, The stimulation signal applied to a single baroreceptive nerve fiber can be monitored in a self-regulating manner. Instead of or in combination with the look-up tables mentioned above, additional memory areas for providing information or signals may be provided, so that, for example, a state estimator / Kalman filter is used for the adjustment, If the preceding signal is to influence the manipulated variable for the adjustment together, the signal itself can also be stored.

  In the following, with reference to FIG. 5, two different blood pressure regulation modes in which the implantable device can influence the blood pressure will be described. In both charts shown in FIG. 5, the upper graphs respectively show the blood pressure along the time axis t. The lower graphs in both figures schematically show the stimulation amplitude of one stimulation signal SSI, respectively. In the case of the blood pressure regulation shown at the top in FIG. 5, it can be seen that immediately after activating and applying the stimulus signal SSI having the stimulus amplitude A3, a depression DE is produced which significantly lowers the blood pressure. If the stimulus signal SSI is repeated at a temporal repetition t1, this will cause the blood pressure to fall quickly until the desired blood pressure value is reached.

  In contrast, blood pressure regulation mode B, illustrated in the lower diagram, provides another natural physiological blood pressure regulation response. Thus, in this case, the stimulation signal SSI is activated and applied at a stimulation amplitude A4 which is considerably smaller than in the case of the stimulation amplitude A3 in the adjustment mode A described above. With such a small stimulus signal amplitude A4, no acute depression DE of the blood pressure value is achieved. In addition, in the case of the adjustment mode B, if the time interval between the individual stimulus signals SSI is chosen to be appropriately large, ie considerably larger than in the case of the mode A (see the time axis in minutes), As is evident from the blood pressure function of the case, it causes a very slow but constant drop in blood pressure. This adjustment mode B, also called "secondary effect" in comparison with adjustment mode A, called "primary effect", can save a lot of energy for the operation of the implantable device. In addition, the load on the nerve tissue and also on the electrodes is significantly lower, in addition to which the blood pressure can be carefully regulated. Both the stimulation amplitude A4 and the temporal repetition rate t2 can be individually selected to adjust the desired blood pressure drop. The manner called adjustment mode B is preferably suitable for the treatment of chronic hypertension, whereas the adjustment mode A, called primary effect, is preferably applied in the case of a hypertensive crisis.

  The implantable device according to this solution can switch its operation between both regulation modes autonomously in response to the occurrence of a particular blood pressure situation, i.e. when it is important to lower the blood pressure peak as fast as possible. Is suitable for the adjustment mode A, and when it is important to gradually correct the blood pressure, the adjustment mechanism B is applied. All of the latest information captured in the lockup table and the information sent to the evaluation / control unit A / S can be used to determine which of the two adjustment mechanisms to apply.

  As already explained in connection with FIG. 4, the n single pulses EP consist of the cathodic and anodic signal parts KT and AT, so that both polarized signal planes are completely mutually in phase with each other. Charge balanced stimulation, which avoids remnant polarization of the electrodes, each of which contributes to the stimulation. Despite this measure, it is not always possible to eliminate the remanent polarization at the electrodes, even if only slightly, which can impair both the pulse shape and the pulse strength of the subsequent stimulation single pulse. It is important to eliminate the undesirable effects caused by this remanent polarization.

  To this end, a further preferred embodiment of the implantable device formed according to the solution comprises an electrode impedance measuring unit EM (see FIG. 1), which comprises an implantable module Or is disposed on the support base 1 and is electrically connected to the electrode device E and the evaluation / control unit A / S. The electrode impedance measuring unit EM is configured to perform an impedance measurement on at least the electrodes of the first electrode device during each of the n single pulses EP, thereby measuring the polarization of the electrodes. The electrode impedance measuring unit EM is further connected to a first depolarizing unit EE1, which is also part of the implantable module or is mounted on the support base 1. The first depolarizing unit EE1 is configured to selectively activate the corresponding electrode by applying an electric signal and temporarily activate the corresponding electrode when the remanent polarization of each electrode is confirmed by the electrode impedance measuring unit EM. The polarization can be depolarized. Not only that, the first depolarization mechanism EE1 can not only capture and correspondingly remove possible remnants of polarization at the electrodes involved in the stimulation during each single pulse, but rather all individual stimulations After the signal SSI, a corresponding polarization measurement and a corresponding active depolarization are performed. As a result, all single pulses EP can be generated with no or at least little polarization effect, whereby all individual stimulation signals SSI are generated by this electrode device under the same electrical conditions. By doing so, it is possible to exclude the stimulus signal from generating the DC potential dominance in the temporal order.

  The implantable device formed according to the present solution comprises, in a preferred embodiment, an electrode device E which is modified with respect to the implantable electrode device E illustrated in FIGS. The electrode device E, illustrated in FIG. 6 and discussed further below, actively promotes signal propagation along baroreceptive nerve fibers in the direction of the heart, which is undesirable but is possible with the electrode devices described above. Can be suppressed.

  To this end, the implantable electrode device is provided with a surface of the support base, which in the implanted state is oriented towards the nerve fiber bundle and is a straight cylinder, with neurons propagating along the nerve fiber bundle in one direction. A third electrode device 7 for inhibiting electric signals is provided. The third electrode device 7, which will be described in more detail below, is activated exclusively or especially in connection with the electrical stimulation of at least one baroreceptive nerve fiber. For this purpose, a second function generator F2 is provided, which is also integrated in the implantable module and has a defined time window T1 (see FIG. 4). Before and / or during the operation, an electrical so-called blocking or blocking signal is generated. The second function generator F2 (see FIG. 1) is further indirectly or directly connected to the second signal-to-current converter SSW2, wherein the second signal-to-current converter SSW2 is The signal is sent to the third electrode device 7. Like the first function generator F1, the second function generator F2 can also generate a single pulse composed of polarizable and repolarizable rectangular partial signals, respectively. Here, too, the polar faces of the two partial signals are neutralized, so that after each single pulse, as little residual remanent polarization at the respective electrode face 9 is left as possible.

  Furthermore, a second modulator M2 is connected between the second function generator F2 and the second signal-to-current converter SSW2, and the second modulator M2 is a rectangular pulse-shaped repolarizable partial signal. The signal gradient trajectory assigned to the AT is expanded and smoothed in time with respect to the polarizable partial signal KT, and the signal strengths assigned to both partial signals are made uniform. The measures associated with the second modulator M2 are performed for the same reasons as described above for the first modulator M1. The second modulator M2 as well as the second function generator F2 are integrated in the implantable module. In the case of the second modulator M2 as well, optionally additionally, the polarizable partial signal in each single pulse is separated from the repolarizable partial signal by a zero signal level which can be generated in the second modulator M2. Can be separated in time. In this way, a long and steep signal gradient between both partial signals is avoided, this long and steep signal gradient being able to excite an inhibitory effect under extraneous electrodes or to additionally stimulate nerve fibers. (So-called anodic break excitement).

  With the third electrode device 7, inhibition can be achieved either by means of a so-called anode block or by application of a sinusoidal signal with a frequency in the kilohertz range, a so-called HF block. In the case of an anode block, at least one of the third electrode surfaces is polarized to the anode, thereby generating a dominant potential at the location of the efferent nerve fiber, which potential stimulates the stimulation of the corresponding nerve fiber. Is suppressed. In this case, no additional modulation by the second modulator M2 is necessary. Similarly, inhibition can be achieved by the application of a high-frequency signal, wherein the application of the high-frequency signal applies a high-frequency electrical inhibition signal at at least one selected third electrode surface, thereby providing efferent nerve fibers. The electrical signal transmission mechanism along will temporarily stop.

  A third electrode device 7 for purposefully inhibiting a stimulation signal propagating in one direction, preferably in the direction of the heart, along at least one selective baroreceptive nerve fiber, also a third electrode device 7 Are connected to an electrode impedance measurement unit EM in order to capture possible remnant polarizations at the electrode surfaces 9, 8 belonging to. A corresponding depolarization of the possible remanent polarization is likewise effected by a second depolarizing mechanism EE2, which is capable of remanent polarization during a single pulse, but also between possible successive inhibition signals. Can also be eliminated by metering the electrical activity of the individual electrodes.

  With regard to EMP protection and magnetic coupling by MRT, a corresponding unit EMP is incorporated in the implantable module for the purpose of electrically protecting the implantable device. This unit monitors the input part of the electrode and permits disconnection when a potential fluctuation is evoked from outside. The EMP unit is additionally equipped with a magnetic field sensor, which activates a temporary self-protection program when capturing a strong DC field.

  FIG. 6 shows a schematic plan view of a preferably formed implantable manchette electrode E, on which the manchette electrode E, preferably made of polyimide, is position-selective for the electrical signals of the neurons. Attached next to the first electrode device 2 provided for detection and selective electrical stimulation of individual nerve fibers is a third electrode device 7 used for inhibiting at least one selected nerve fiber. ing. To avoid repetition, reference is made to the above description of FIGS. 2a and 2b for a description of the individual electrodes of the first electrode device 2 and of the second electrode device 12.

  A third electrode device 7, which inhibits efferent, here signal propagation along nerve fibers to the heart H, comprises two axially separated third electrode strips 8 and a third electrode Between the strips 8, a third electrode structure 13 is provided in the middle, the third electrode structure 13 comprising four third electrode surfaces 9 arranged separately from one another. All the electrodes 8, 13 of the third electrode device 2 are connected to the evaluation / control unit A / S via an electrical conductor L which is mounted on or integrated into the support base 1. Connected or connectable. The electrical conductor path L can optionally be provided with a detachable connection structure V.

  The third electrode device 2 optionally comprises an optical light-guiding device 10, which comprises four separate light-guiding ports 11, each distributed in the circumferential direction U. Contains. The light guides LI to the individual light guides or apertures 11 run in the support base 1 and along certain nerve fibers are selectively stimulated and / or activated by optogenetics. The central side can be combined with one uniform light source LQ or a separate light source LQ with different light wavelengths to cause activated selective inhibition.

  The selection of the geometry and the size of the individual electrodes, i.e. the first and third electrode strips 5, 8 and the first and third electrode surfaces 4, 9 can basically be made individually and in synchronization with one another. In particular, it depends on the diameter of the nerve fiber bundle around which the implantable manchette electrode E can be applied. In other words, the extent of the first and third electrode structures and electrode strips and possibly the optical waveguide device 10 oriented in the circumferential direction U corresponds to the length of the periphery of the nerve fiber bundle around which the Manchette electrode E is wound. Is preferred. The axial distance of the triode electrode device is preferably adapted to the diameter of the so-called Lanvier constriction at the myelinated nerve fiber of the nerve fiber to be excited and the resulting distance. In the exemplary embodiment shown in FIG. 6, the electrodes are shown as rectangular electrode surfaces. In an advantageous manner, that is to say in particular to avoid field line densification occurring at the rectangular edges of the electrode, it is proposed to form the electrode surface with at least rounded corners.

  Therefore, in the case of humans, it is important to inhibit or activate myelinated fibers of a particular size. This is only possible along the nerve fiber, where this fiber is not myelinated, ie at the so-called Lanvier's annulus. As the diameter of the nerve fibers increases, the spacing between the rings, or axial distance, of the Ranvier rings increases and, correspondingly, the Ranvier rings of very large fibers reach a sufficiently high statistical probability. It is important that the axial distance between the two axially separated first electrode strips 5 is selected to be approximately the same length as or slightly greater than the axial distance of the hoop. Corresponding to this is preferably applied also to the axial separation of the third electrode strip 8.

  The overall axial extent of the entire manchette electrode E is adapted to the ratio of the size of each nerve fiber bundle within the body, and typically should not exceed 4 cm.

  The reference electrode surface 12 attached to the back surface of the support base 1 is used for capturing electrocardiogram signals and, if necessary, noise levels captured in the body.

  In addition, the support base 1 has at least one, preferably two or three, openings 14 reinforced by a metal ring structure, which openings 14 allow the implanted electrode device CF to be connected to the nerve. Used to fix to fiber bundles. The fixation is performed using a surgical thread, each of which is passed at least once through the opening 14 and sutures the tissue surrounding the nerve fiber bundle with the surgical thread. Of the support base, the first and second electrode devices 2 and 7 are mounted, so that when implanted, these electrode devices form a straight cylindrical shape that contacts the surface of the nerve sheath of the nerve fiber bundle. Unlike the rolled area 1B, the support base 1 adjacent to the support base area 1B protrudes laterally from the nerve fiber bundle like a flat flag and protrudes into the surrounding tissue. The metal ring structure 14 assists in reliably mechanically receiving the securing force acting along the surgical thread and preventing the support base from being damaged and cut.

  In order to wrap the implantable electrode device E in a manchette manner around the nerve fiber bundle, which is also not shown, the third electrode structure 7 must be arranged on the side H to the heart along the nerve fiber bundle. Must. The first electrode device 2 used for the selective detection and also the selective stimulation of the located nerve fibers is attached to the brain side G along the nerve fiber bundle.

  The first and third electrode strips 5, 8 and the first and third electrode surfaces 4, 9 are preferably deposited or sputtered on a support base, and strengthening by galvanic treatment is conceivable. Laser structuring of thin metal films is also a technology. In particular, in order for the first and third electrode strips 5, 8 to be permanently bonded to the support base 1, the electrode strips have a local opening 15 (see FIG. 7a), The polymeric material of the support base 1 at least partially passes through or projects into the opening. Otherwise, the electrode surfaces 16 of the first and third electrode strips 5, 8 are otherwise arranged flush with the upper surface 1 'of the support base and directly contact the surface of the nerve fiber bundle.

  In order to permanently improve the bonding of the electrode strips 5, 8, one preferred exemplary embodiment proposes that the electrode strips be integrated into the support base extensively as follows (for which: See FIG. 7b).

  Each of the electrode strips 5, 8 has a metal substrate 17 having an upper surface 18 and a lower surface 19. Structural elements 20, preferably in the form of pillars, ribs, girders, or sleeve-like protrusions, which are distributed in a plane and rise vertically, preferably on the upper surface 18, preferably over the entire upper surface, Provided integrally, the structural element 20 has a surface area 21 facing the support base surface 1 ′, which surface area 21 can be directly applied to the nerve sheath of the nerve fiber bundle. it can. In addition, it is advantageous to provide an adhesion mediating layer 22 at least between the lower surface 19 and the polymer material of the support base 1 surrounding the substrate 17. The adhesion mediator layer 22 can additionally be applied on the upper surface 18. Particularly suitable adhesion mediator layers consist of silicon carbide (SiC) and diamond-like carbon (DLC). Preferably, the electrode strips 5, 8 are made of iridium oxide, which can be considered as one of the materials having the highest charge transfer capacity.

  A further refinement for forming the structural elements 20 distributed and mounted on the upper surface of the substrate 17 is illustrated in FIG. 7c. FIG. 7c shows a longitudinal section of a structural element 20 having a longitudinal extension LA oriented perpendicular to the upper surface 18 of the metal substrate 17 along which at least one of the structural elements 20 extends. Has two second surface regions 23, which are oriented parallel to the upper surface 18 of the metal substrate 17, and on which the adhesion mediating layer 22 or attachment media layer arrangement 22 'is attached. The second surface region 23 is spaced apart from the first surface region 18 and is separated by an adhesion-mediating layer (22) or an adhesion-mediating layer configuration (22 ') and completely by a biocompatible polymer. It is surrounded. The second surface area is oriented towards the upper surface 18 of the substrate 17, as is evident from FIG. 7c. Of course, in addition to this, also in the third surface region 24 opposite the second surface region 23 and / or in the upper and / or lower surfaces 18, 19 of the substrate 17, the adhesion-mediating layer 22 or the adhesion-mediating layer structure 22 ′ Can be provided and is advantageous.

  The number and / or arrangement of the individual structural elements 20 can be chosen arbitrarily, but is preferably a geometrically aligned positional relationship KO, as is evident from FIG. Or a more polygonal arrangement pattern is suitable.

  8a to 8f show a manchette M partially embracing the support base 1 of the implantable manchette electrode CE, which is directly in the support base area 1B of the support base 1. Unlike the support base region 1B, unlike the support base region 1B, the material does not spontaneously deform into a straight cylindrical shape due to the mechanical prestress inherent in the material. It holds the area applied to the nerve sheath on both the lower and upper surfaces.

  Manchette M primarily improves the handling of implantable manchette electrodes CE, which require the surgeon to take particular care, based on the very small thickness of the support base and the delicate electrode device mounted on the support base surface Used to The manchette M is preferably formed in a unitary structure and has a lower manchette Mu and a upper manchette Mo, both of which are articulated via a film hinge joint 25 (for this purpose). 8b and 8c). The lower portion of the manchette Mu has a concave portion 26 in which the support base 1 is embedded, and the support base 1 can be fitted into the concave portion 26. In the fitted state, the lower manchette Mu holds the support base 1 in a fringing manner that is evident from FIG. 8 b, ie the lower manchette MU protrudes from the side under the support base 1.

  The upper and lower manchettes Mo, which are integrally connected to the lower and upper manchettes Mu via the hinge joints 25, have a shape and a size suitable for the lower and upper manchettes Mu, and have recesses 27 for embedding the support base 1 in the same manner as the lower and upper manchettes Mu. Therefore, in the closed state of the manchette M, the support base 1 is closed and held as shown in FIG. 8A, and only the support base region 1B protrudes from the manchette M.

  The manchette M is used not only to improve the handling, but also in particular to better secure the manchette electrode CE to nerve fiber bundles. To this end, the upper and lower Mo and Mu sides of the manchette each have a fixed opening 14 '(see FIGS. 8a, 8b and 8d), and these fixed openings 14' are in the folded state. In the manchette M, it fits tightly with the fixed opening 14 mounted in the support base 1. In this way, the surgical thread 28 can be passed through the openings 14, 14 'of the manchette electrode CE held by the manchette M. Thereby, the load on the fixed opening 14 covered with the metal ring of the manchette electrode CE can be reduced by the fixed opening 14 ′ attached in the manchette M. The Manchette M is preferably made of a stable plastic material, for example Parylene. To further increase strength, Mo and Mu may consist of a polymer hybrid (eg, parylene (inside) and silicone rubber outside). This hybrid has the advantage of combining the stability of parylene with the tear strength of silicone. In a preferred embodiment, the fixed openings 14 'in the manchette M are implemented reinforced with a corresponding material thickening.

  An opening window 29 for ensuring free access to the reference electrode surface 12 is attached to the upper part of the manchette Mo. FIG. 8e shows a short section of the support base 1 embraced by the manchette M in this regard, on which the reference electrode surface 12 is mounted, An open window 29 mounted in the upper Mo remains freely accessible. The opening window 29 preferably embraces the reference electrode surface 12 at an obliquely falling boundary gradient 29 ′, whereby the reference electrode surface 29 is entirely in body contact with the surrounding tissue.

  In order to ensure that the manchette M remains closed, a latch lock structure V composed of, for example, a pin 30 and a concave portion 31 arranged opposite to each other is arranged between the upper and lower parts Mo and Mu of the manchette. (See FIGS. 8c and 8f). When the upper and lower portions of the manchette are folded, a force is applied to the pins 30 to fit into the corresponding recesses 31, and the pins 31 are respectively permanently held in the recesses 31 by frictional coupling. FIG. 8 illustrates a closed state of the latch lock structure V. In this case, the pins 30 mounted on the upper part of the manchette Mo penetrate through the corresponding openings mounted on the support base 1 and reach the concave part 31 of the lower part of the manchette Mu on the end side. Of course, alternatives to the latch lock structure are conceivable, for example in the form of a suitably formed locking mechanism.

  FIG. 9 illustrates a further embodiment which allows easy implantation of the manchette electrode CE formed according to the present solution. A fluid path system 32 is incorporated in the support base 1, and the fluid path system 32 is completely held by the support base 1. The fluid path system 32 extends substantially into the region of the support base region 1B, which, due to the prestresses inherent in the material, forms a straight cylindrical shape by independent self-winding without the influence of external forces. I have. On the other hand, when the fluid channel system 32 is filled with a fluid, preferably water, the water pressure formed along the fluid channel system 32 stretches the support base region 1b flat against the winding force inherent in the material. be able to. For this purpose, the fluid path system 32 has fluid path branches 33 running in the circumferential direction of a spontaneously formed straight cylindrical jacket surface, and these fluid path branches 33 are filled. In this state, the necessary extension is forcibly applied to the support base region 1B.

  In order to fill the fluid passage system 32, at least two passage openings 34 are provided in the support base 1, and the size and arrangement of the passage openings 34 are determined so that the passage openings 34 do not leak fluid. It is designed to communicate with the inlet and outlet of a running fluid inlet or outlet pipe 35,36. The inlet or outlet pipes 35, 36 running in the manchette M are fluidly connected to a fluid control system 37 operable by the operator.

  When implanting, the fluid channel system 32 is filled with fluid, thereby extending the support base region 1B. In this state, the operator places the manchette electrode CE exactly at a predetermined site along the nerve bundle. Thereafter, the operator empties the fluid channel system 32, whereby the support base region 1B spontaneously wraps around the nerve fiber bundle. As a last step, the manchette electrode CE is fastened to the surrounding tissue with a surgical thread by means of a fixed opening 14 'in the manchette.

  In an advantageous form of the fluid channel system 32 described above, it is contemplated that the fluid channel system 32 is filled with a shape memory metal-shape memory polymer. The channel opening 34 is provided with a metallized contact for activation purposes, via a correspondingly modified control device 37 via this contact in order to deploy the implantable electrode device CE. A voltage can be applied along the lead-in tubes 35, 36 until the electrodes are finally placed.

  FIG. 10 shows a flow diagram that can clarify the effect on blood pressure or the order of the individual steps with respect to blood pressure regulation by selectively electrically stimulating nerve fibers. Assume that for stimulation purposes, an electrode device capable of the inhibitory function illustrated in FIG. 6 is applied locally around the vagus nerve. If this is not the case, then the electrode device according to FIG. 2a is suitable. The following description simultaneously relates to the components shown in FIG. 1 of the implantable device E according to the solution. To avoid repetition, it should be mentioned in advance that the decision point represented by y corresponds to "yes" and the decision point represented by n corresponds to "no".

  I) Start: Activation of the implantable device E either manually or automatically. For this, an evaluation / control unit in the form of a microcontroller is activated (A / S, FIG. 1).

  II) Capture of the electrocardiogram signal by the electrode 12 of the Manchette electrode E (see FIG. 6). In this case, the evaluation / control unit A / S authenticates the R-wave and separates any EMP errors from the signal, with a plurality of cycles being monitored. In this connection, the evaluation / control unit A / S determines the reliability and recognizes the R-wave with this reliability. Finally, the evaluation / control unit A / S determines the heart rate.

  III) Capture of the blood pressure signal SN by the first electrode surface 4, the first electrode band 5, and the electrocardiogram electrode surface 12 of the Manchette electrode E. This is done by coherently averaging the signals in the middle row of the first electrode surface 4, triggered by a predefined rising gradient of the electrocardiogram signal.

  IV) Determine if a blood pressure change is present.

  IVa) In this connection, the evaluation / control unit A / S queries the latest reference blood pressure (SB) and compares or calibrates the amplitude of the reference signal with the blood pressure signal SN.

  IVb) If there is a change in blood pressure, authenticate the blood pressure and the stimulation location (see y). The evaluation / control unit A / S queries the look-up table LT for the blood pressure signal values SN and the time intervals ZV and ZV * which have already been filed for this patient and retrieves them in the course of averaging. Compare with SN. The evaluation / control unit A / S determines the "best" SN of the electrode and marks that electrode as a subsequent stimulation electrode in the working memory.

V) Determine the time lag ZV between the electrocardiogram signal and the blood pressure reference signal. In this case, the comparison unit K1 determines the time lag ZV between the R wave, the rising threshold, and the reference blood pressure.
The comparison unit K2 determines a time lag ZV * between the rising threshold of the reference signal and the blood pressure signal of the neuron captured via the electrodes (see ZS in FIG. 3 and SN in FIG. 4). The start P1 and the end P2 of the pulse wave PW are determined from the reference blood pressure. This interval is defined as T1 (see also FIGS. 3B and 3C). The interval T1 is shifted by a time shift ZV + ZV * to be an interval ZF. (See Fig. 3)

VI) Determination of stimulation and selection of stimulation parameters The evaluation / control unit A / S determines the time UH and the current posture and movement of the patient by means of an acceleration sensor (BS). The evaluation / control unit A / S further determines the impedance of the stimulation electrodes via the interstimulus impedance detector. The evaluation / control unit A / S determines whether stimulation is to be performed, yes (y) or no (n), based on the elevated blood pressure value, the heart rate, the activity of the patient and, for example, a wireless communication module (SES). ), No failure signal of an implant component (e.g., the stimulating IC), or a conflicting control command triggered by detection of a strong static magnetic field (EMP) is not issued. I do.

VIa) Stimulus reference value. The evaluation / control unit A / S compares the raised parameters with the parameters already stored in the look-up table LT and the memory module SM and selects the appropriate stimulation parameters (suitable for determining the blood pressure). (meaning how "strong" and how "long" must be stimulated to reduce x%).
(Inform the "active" function generator F1 (binary) of the stimulus coordinates, such as ZF, number and shape of the pulses. If parallel inhibition is required, appropriate Important stimulus parameters to the function generator F2 (binary).

  VIIa) The evaluation / control unit A / S decides on the inhibition method (HF block or anode block).

  VIIb) The evaluation / control unit A / S makes a decision on the stimulation mode A or B (see FIG. 5).

VIIIb) Preparation / modulation of active stimulus parameters based on mode A When A mode is selected for fast intervention, a fixed stimulus sweep with a defined number of single pulses is provided (length is defined as ZF interval and This stimulus sweep is repeated with a predetermined interruption (see mode A in FIG. 5).
The evaluation / control unit A / S passes the template to the first function generator F1, which generates a voltage signal and transmits this voltage signal to the modulator M1.

VIIIc) Preparation / modulation of active stimulus parameters based on mode B Once the B mode is selected, the single pulse must be further optimized. The first function generator F1 creates a similar template of the stimulus interval (SSI) and fits a defined number of individual biphasic pulses into the interval ZF. In this case, the stimulation signal is adapted to the biological signal. The reference blood pressure trajectory is overlaid on the amplitude of a single pulse as a wrapper function (see FIG. 4A). The first function generator F1 passes a table with the prepared stimulus sweep to the modulator M1.

IX) Sweep Single Pulse Phase Adaptation Modulator M1 is responsible for both modes and both all individual pulses to create an ideal single pulse shape for the individual patient. (See FIG. 4B). Modulator M1 passes the "finished" voltage signal in the form of a sweep to a signal-to-current converter (SSW1).

Xb) Performing Active Stimulation The signal-to-current converter SSW1 waits for an ECG trigger signal and waits until an "Activation Window for Stimulation ZF" is reached, and then transmits a stimulation sweep to a preselected stimulation electrode. During each single pulse, the impedance of the stimulation contact is captured by the electrode impedance measurement unit EM. When the polarization is detected by the evaluation / control unit A / S, the evaluation / control unit A / S stimulates the active polarization compensator EE1 with a small additional charge for compensation during each pulse. Gives a command to transmit by the unit. If the inter-stimulus compensation is not sufficient, the inter-sweep compensator is additionally activated after the end of the sweep to cancel the polarization.

VIIIa) Preparation / modulation of inhibitory stimulation parameters The evaluation / control unit passes the stimulation interval for inhibition to the function generator F2. Generally this is longer than the active stimulus, ie it begins shortly before the active stimulus and ends after the active stimulus.
The evaluation / control unit A / S specifies whether the second function generator F2 applies only anode blocks, ie single-phase blocks, or whether HF blocks are to be performed. The function generator 2 additionally creates a stimulus (voltage) template accordingly. In the case of the HF block, F2 passes a voltage signal to modulator M2 to "smooth" the individual phases.

Xa) Implementation of Inhibitory Stimulation The signal-to-current converter SSW2 converts the signal either as an anode block of F2 or as an HF block of M2 into a current signal, The signal is transmitted via the electrode 9 (see FIG. 6). The electrode impedance measuring unit EM monitors the polarization of the inhibiting electrode 9 and, if necessary, activates the depolarizing unit EE2 for compensation via the evaluation / control unit A / S.
In the case of the HF block, both inter-stimulus and inter-sweep can be performed; in the case of the anode block, only the inter-sweep compensator is active.

XI) Evaluation of the stimulus The evaluation / control unit A / S determines the change in the blood pressure curve and starts the iteration. In the case of the B mode, the number of heartbeats at which the stimulation is interrupted can be variously changed as a main stimulation parameter. This function provides (patient specific) feedback on how the implant works.
The outcome of the stimulus is entered into memory for later comparison.

DESCRIPTION OF SYMBOLS 1 Support base 1 'Support base surface 1B Support base area 2 1st electrode device 3 1st electrode structure 4 1st electrode surface 4a Spread of 1st electrode surface in the axial direction 4U Circumferential direction of 1st electrode surface 5 First electrode band 6, 6 ′ Signal detection and generator 7 Third electrode device 8 Third electrode band 9 Third electrode surface 9a Axial spread of third electrode surface 9U Spread of the third electrode surface oriented in the circumferential direction 10 Optical waveguide device 11 Optical waveguide port 12 Second electrode device, electrocardiogram electrode surface 13 Third electrode structure 14 Fixed opening 15 Opening 16 Electrode band surface 17 Substrate Reference Signs List 18 upper surface 19 lower surface 20 structural element 21 surface region 22 adhesion mediating layer 22 'adhesion mediating layer configuration 23 second surface region 24 third surface region A axial direction A / S evaluation / control unit A3, A4 amplitude A ax Maximum amplitude AT Anode side signal part BS Acceleration sensor DE Depression E Implantable electrode device, manchette electrode E1 Anode side amplitude E2 Cathode side amplitude E3 Cathode side pulse width E4 Anode side amplitude E5 Repetition rate E6 Repolarization gradient E7 Zero level between the anode side and cathode side amplitudes EE1, EE2 Depolarization unit EKG Electrocardiogram time signal EM Electrode impedance measurement unit EMP Protection unit against electromagnetic pulse action EMP / MRT EP Single pulse ES Energy storage / energy source F1, F2 Function generator G Brain H Heart KO Geometric positional relationship KT Cathode side signal part L Conductor path LA Longitudinal axis of structural element LI Optical waveguide LQ Light source LT Lookup table M Maximal M1, M2 Modulator NF Nerve fiber NFB Nerve fiber bundle P1, P2 Characteristic phase point along time signal PW pulse wave, blood pressure wave R R wave of electrocardiogram signal SB blood pressure sensor SES signal and energy supply unit SM memory module SN Natural neuron electric signal SSI stimulation signal SSW1, SSW2 Signal-current converter T Timer unit T1 Duration of pulse wave T _SN Pulse length of natural neuron electric signal U Circumferential direction UH clock V Connection structure ZF Time window ZS Time signal ZV, ZV * Time shift

Claims (40)

Implantable device for position-selective capture of electrical signals of neurons propagating along at least one nerve fiber contained in a nerve fiber bundle and selective electrical stimulation of said at least one nerve fiber Wherein the implantable electrode device (E) is arranged on a biocompatible support base (1) that can be applied in a manchette fashion around the nerve fiber bundle, A compatible support platform (1) has a straight cylindrical support platform surface (1 ′) oriented towards the nerve fiber bundle in the implanted state, wherein the support platform surface (1 ′). ) Includes a first electrode device for position-selective capture of electrical signals of said neurons and selective electrical stimulation of said at least one nerve fiber. Implantable electrode device (E) on which a second electrode device (E) for capturing an electrocardiographic signal is arranged, wherein said second electrode device (E) is arranged on said biocompatible support base (1). )When,
An evaluation / control unit (A / S) electrically connectable or connected with said implantable electrode device (E), said electrical signals of said neurons captured selectively and said electrocardiogram. signal, and decomposition time, and can be evaluated as time signals of neurons in the correlation may be calculated for the physiological parameter, evaluation / control unit (a / S),
A first comparison unit (K1) connected to the evaluation / control unit (A / S), wherein the first comparison unit (K1) comprises a signal between the electrocardiogram signal and a time signal of the neuron correlated with the physiological parameter; A first comparison unit (K1) capable of determining a characteristic and relative time shift;
A first function generator (F1) connected to the evaluation / control unit (A / S), the first function generator (F1) being determined by the evaluation / control unit (A / S) based on the relative time lag; A time window consisting of a number n of single pulses (EP) whose phase and temporal amplitude trajectories are adapted to the calculated neuron time signal correlated with the physiological parameters A first function generator (F1) for generating a stimulated stimulus signal;
A first signal-to-current converter (SSW1) indirectly or directly connected to said first function generator (F1) and said first electrode device (2), wherein said at least one A first signal-to-current converter (SSW1) for transmitting said stimulation signal for selectively electrically stimulating nerve fibers to said first electrode device (2). A control unit (A / S), the first comparison unit (K1), the first function generator (F1), and the first signal-to-current converter (SSW1) are integrated as an implantable module Are implantable devices. At least one second comparison unit (K2) is connected to the evaluation / control unit (A / S);
The second comparison unit (K2) compares at least one signal level assigned to a time signal of the neuron correlated with the physiological parameter with a reference signal to generate a level difference value; The implantable device according to claim 1, wherein the evaluation / control unit (A / S) defines at least the temporal amplitude trajectory of the stimulation signal based at least on the level difference value. .   The implantable electrode device (E) is positioned along the nerve fiber bundle on the support base surface (1 '), which is oriented toward the nerve fiber bundle in the implanted state and is a straight cylinder. 3. Implantable device according to claim 1 or 2, comprising a third electrode device (7) for inhibiting electrical signals of directionally propagating neurons.   The implantable module comprises an electrical energy storage (ES) and / or an induction-based signal and energy supply unit (SES), wherein the induction-based signal and energy supply unit (SES) has at least the evaluation 4. The implantable device according to claim 1, wherein the implantable device is electrically connected to a control unit (A / S). An acceleration sensor (BS) is incorporated in the implantable module and / or an implantable acceleration sensor (BS ′) is provided separately from the module; and 5. Implant according to claim 1, wherein BS, BS ′) generate acceleration information and are electrically connected to the evaluation / control unit (A / S). Possible device. The first function generator (F1) can generate a single pulse composed of a rectangular pulse-like partial signal, which is polarizable and repolarizable, respectively; and the first function generator (F1) and the first pulse A first modulator (M1) is connected between the signal-to-current converters (SSW), and the first modulator (M1) is assigned to the rectangular pulse-shaped repolarizable partial signal. 6. The signal gradient trajectory according to claim 1, wherein the signal gradient trajectory is expanded and smoothed in time with respect to the polarizable partial signal, and the signal strengths assigned to both partial signals are made uniform. An implantable device according to any one of the preceding claims. A second function generator (F2) is provided, which is connected to the evaluation / control unit (A / S), wherein the second function generator (F2) is arranged in time before the determined time window. And / or during the generation of an electrical block signal, and wherein said second function generator (F2) is indirectly or directly connected to a second signal-to-current converter (SSW2); 4. The implantable device according to claim 3 , wherein two signal-to-current converters (SSW2) send the electrical block signal to the third electrode device (7). The second function generator (F2) can generate a single pulse composed of rectangular pulse-shaped partial signals each of a polarizable and a repolarizable, and the second function generator (F2) and the second A second modulator (M2) is connected between the signal-to-current converters (SSW2), and the second modulator (M2) is assigned to the rectangular pulse-shaped repolarizable partial signal. 8. The signal gradient trajectory according to claim 7, wherein the signal gradient trajectory is expanded and smoothed in time with respect to the polarizable partial signal, and the signal strengths assigned to both partial signals are made uniform. Implantable device. The implantable device according to claim 8, wherein the second function generator (F2) and the second modulator (M2) are integrated in the implantable module.   The first or second modulator (M1, M2) generates the polarizable partial signal for each single pulse by means of the zero signal level that can be generated by the first modulator (M1). 9. The implantable device according to claim 6, wherein the implantable device is configured to be temporally separated from the partial signal. An electrode impedance measurement unit (EM) is part of the implantable module or is arranged on the biocompatible support base (1), the electrode device (E) and the evaluation / control unit (A) / S) and the electrode impedance measurement unit (EM) performs an impedance measurement on at least the electrode of the first electrode device (2) during each of the n single pulses. An implantable device according to any of the preceding claims, characterized in that it is performed. An electrical depolarizing mechanism (EE) is part of the implantable module or is located on the biocompatible support base (1), the electrode device (E) and the evaluation / control unit ( A / S), and the depolarizing mechanism (EE) selectively applies an electric signal when remanent polarization at each electrode is confirmed by the electrode impedance measuring unit (EM). The implantable device of claim 11, wherein the remanent polarization depolarizes the remanent polarization. A separate blood pressure measurement system (SB) is provided for capturing the absolute blood pressure value, the absolute blood pressure value being provided via the guidance-based signal and energy supply unit (SES) to the evaluation / control unit (A). / S), and wherein the evaluation / control unit (A / S) is adapted to provide the absolute blood pressure value, the electrocardiogram signal, a time signal of the neuron correlated with the physiological parameter, and at least one of: The implantable device according to claim 4, characterized in that the first function generator (F1) is controlled to generate the stimulation signal based on a reference signal. A memory unit is provided in the form of a look-up table, said memory unit being part of said evaluation / control unit (A / S) or as a separate unit; ), And
14. The memory unit according to claim 2, wherein at least one of the following information: level difference value, acceleration information, and captured absolute blood pressure is storable and retrievable in the memory unit. An implantable device according to claim 1. The support base surface (1 ′), which is directed toward the nerve fiber bundle and is a straight cylindrical shape, has an axial (a) and circumferential (U) oriented spread; The first electrode device (2) is attached to a support base surface (1 ′), and the first electrode device (2) is
An axial arrangement of at least three first electrode structures (3), each with at least two first electrode surfaces (4) arranged circumferentially;
-Including at least two first electrode strips (5) axially spaced from one another and extending in the circumferential direction, each being in the form of a ring, said first electrode strips (5) comprising: 4. The implantable device according to claim 3 , wherein the at least three electrode structures are sandwiched on both sides in the axial direction and are connectable or connected to the evaluation / control unit (A / S). Device. The third electrode device (7) is axially aligned with the first electrode device (2) on the support base surface (1 '), which is straight cylindrical toward the nerve fiber bundle; At least two third electrode strips (8), which are arranged next to each other in the axial direction, are axially separated from each other, extend in the circumferential direction (U), and each have a ring shape;
At least one including at least two third electrode surfaces (9) each distributed in the same manner in the circumferential direction between the axial directions of the at least two third electrode strips (8); The implantable device according to claim 15, characterized in that it comprises a third electrode structure (13). Said first and third electrode surface (4, 9) is, along an imaginary circular line, respectively in the circumferential direction (U), characterized in that it is arranged dispersed in the same way according to claim 1 6 Implantable device. Said first and third electrode surfaces (4, 9) having extensions oriented in the axial direction (4a, 9a) and in the circumferential direction (4U, 9U), respectively;
The extent (4a, 4U) of the first electrode surface (4) is the same,
The extent (9a, 9U) of the third electrode surface (9) is the same, and the extent (9U) of the third electrode surface (9) oriented in the circumferential direction is the first extent. 17. Implantable device according to claim 16, characterized in that it is larger than the circumferentially oriented extent (4U) of the electrode surface (4) of the device.   19. The implantable device according to claim 18, wherein the axial extent (4a, 4U) of the first and third electrode surfaces (4, 9) is the same.   17. The support base surface (1 ') to which the first and third electrode devices (2, 7) are attached is formed integrally, that is, without interruption. 20. The implantable device according to any one of claims 1 to 19. The axial distance between the first electrode strips (5) is selected to be greater than or equal to the axial distance of the third electrode strip (8); and the axis between the third electrode strips. implantable device of claim 1 6 the distance direction, and measuring between 0.5Cm～3cm. The first and third electrode strips (5, 8) have the same shape and size;
The area of each of the first and third electrode surface (4,9), according to claim 1 6, respectively, wherein the smaller again that than the area of the first or third electrode zone (5,8) Implantable device. The first electrode surface (4) is made of a metal material, and the metal material has a higher charge transfer capacity than the material forming the third electrode surface (9). An implantable device according to claim 16 . It is said metal material is iridium oxide of the first electrode surface (4), and / or claims wherein the material of said third electrode surface (9) is characterized in that platinum, or a conductive polymer Item 24. The implantable device according to item 23. The first and third electrode devices (2, 7) are each operable as a three-electrode device, ie the first and third electrode bands are respectively the first and third electrode structures. The implantable device according to claim 16, characterized in that it is polarizable to the opposite polarity with respect to (3,13). The third electrode device (7) comprises at least one optical light-guiding device (10), wherein the at least one optical light-guiding device (10) is distributed in a circumferential direction (U). An implantable device according to claim 16, characterized in that it comprises at least two separate optical waveguide ports (11) arranged in a manner. The at least two separate optical waveguides (11) are equally distributed along an imaginary loop line, and the optical waveguides (11) are axially (11a) and circumferential, respectively. 27. A spread according to claim 26, having a spread oriented at (11U), said spread corresponding to that spread (9a, 9U) of the third electrode surface (9). Implantable device. The first electrode surface (4) and the first electrode band (5) of the first electrode device (2) and the third electrode surface (9) of the third electrode device (7); The device according to claim 16, characterized in that the third electrode strips (8) are each mounted on the support base surface (1 ') so as not to protrude from the support base surface (1'). Implantable device. The biocompatible support base (1) is made of at least one biocompatible polymer, and is at least a portion of the support base surface (1 ′) that is straight cylindrical toward the nerve fiber bundle. 29. The implantable device according to any one of claims 1 to 28, further comprising an agent that inhibits an inflammatory response. 17. The implantable device according to claim 16 , wherein the biocompatible support base (1) contains a biocompatible polymer. The first and / or third electrode strips (5, 8) each have at least one local opening, and the first and / or third electrode strips (5, 8) are 31. The implantable device according to claim 30 , wherein a biocompatible polymer is planarly associated with the support base surface (1 ') so as to at least partially penetrate the at least one opening. Device. 32. At least two reference electrode surfaces (12) are attached to the biocompatible support base (1) on the back side of the support base surface (1 '). An implantable device according to claim 1. Wherein the biocompatible support base (1) is in the region of the nerve fiber bundle headed oriented and has a straight cylindrical the support base surface (1 '), wherein the biocompatible support base (1) Has an edge region (14), each of which has an axially facing base thickness greater than the other support base region, and wherein said edge region (14) has a rounded edge edge. 33. The implantable device according to any one of clauses 1 to 32.   Wherein said biocompatible support base (1) has at least one opening (15) completely penetrating said support base in an area of the support base that cannot be applied in a manchette fashion around said nerve fiber bundle. An implantable device according to any of the preceding claims, characterized in that it is an implantable device.   35. The implantable device according to claim 34, wherein the at least one opening (15) is at least partially coated with a metallic material. A first and / or third electrode strip (5, 8) each having a flat upper surface and a lower surface, and a metal electrode strip base having at least one structural element projecting locally perpendicular to said upper surface; Has,
The flat surface of the metal electrode base is oriented parallel to the support base surface, and the electrode base is oriented toward the support base surface of the at least one structural element. 31. The implantable device according to claim 30, wherein the implantable device is completely surrounded by the biocompatible polymer except for a surface area that does not protrude from the support platform surface.   37. The implantable implant of claim 36, wherein an adhesion mediating layer or an adhesion mediating layer configuration is attached between at least the lower surface of the electrode platform and the biocompatible polymer of the support platform. device.   A plane facing the one surface area or the surface area of the at least one structural element is oriented parallel to the support base surface, and the surface area is free from a side of the support base surface. 38. The implantable device according to claim 36 or 37, wherein the device is accessible and the at least one structural element is integrally connected to the electrode platform.   37. The method according to claim 36, wherein a plurality of structural elements are provided which are geometrically identically distributed on the upper surface of the metal electrode base and are identically formed. 39. The implantable device according to any one of claims 38.   40. The implantable device according to any one of claims 36 to 39, wherein the at least one structural element is shaped like a column, a rib, a sleeve, or a girder.

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